Synthesis of fungicidal morpholines and isochromenopyridinones via acid-catalyzed intramolecular reactions of isoindolinones

Abstract

Acid-catalyzed intramolecular cyclization or rearrangement of isoindolinone derivatives is described. 3-Hydroxy/ethoxy-3,4-dihydro-6H-[1,4]-oxazino-[3,4-a]-isoindol-6-ones are obtained in moderate to good yields. Further acid-catalyzed intramolecular rearrangement reactions give 6H-isochromeno-[4,3-b]-pyridin-6-ones. The mild reaction conditions with convenient starting materials show broad substrate scope and provide the target compounds as novel pesticide leads with good fungicidal or systemical acquired resistance activities.

---

Introduction

Nitrogen- and oxygen-containing heterocyclic compounds are widely found in natural products, drugs and agrochemicals. As important heterocyclic molecules, morpholines, isoindolinones and isochromenones show a wide range of applications in the fields of medicine, agriculture and materials science. For instance, the natural alkaloid lennoxamine contains isoindolinone.¹ Antibacterial drug levofloxacin contains a morpholine structure.² Chelonin A with anti-inflammatory activity³ and acotatarin A with antioxidant activity are also morpholine derivatives.⁴ As biological isochromenone chemicals, altenariol is a new lead compound with herbicidal activity for weed control,⁵ and isochromenopyridinone is used as the iridium ligand for OLEDs (Fig. 1).⁶

Fig. 1 Representative derivatives of isoindolinone, morpholine or isochromenone.

Due to the wide applications of morpholines, construction of their core skeleton has attracted considerable attention.⁷ The most common approach for the synthesis of the morpholine ring is the intramolecular cyclization of a substituted 1,2-amino alcohol. Compared to the base-mediated S_N2 reaction,⁸ transition metal-catalyzed synthesis draws more and more attention;⁹ for example, Soklou et al. reported a gold-catalyzed method for the cyclization of tertiary alcohols with terminal alkyne to yield morpholine-containing aza-spirocycles;^9a Borah and co-workers reported palladium-catalyzed intramolecular cyclization of nitrogen-tethered alkenols to substituted morpholines;^9b the Morandi group reported that an iron salt-catalyzed aliphatic ether metathesis reaction could be utilized to furnish the morpholine core (Scheme 1a).^9c On the other hand, isochromenopyridinones could be prepared in moderate yield by treating the diazonium salt of anthranilic acid in the presence of TiCl₃ with 3-hydroxypyridines in aqueous hydrochloric acid.¹⁰ Among the preparation methods for isochromenopyridinones, rearrangement of isoindolinones showed the highest yield; however, the starting material of isoindolinone is relatively complex with the substrate scope limited only to three fused aromatic heterocycles (Scheme 1b).¹¹ Therefore, the development of synthetic methods for isochromenopyridinones with improved efficiency is necessary. There are various methods for the synthesis of isoindolinones.¹² Among them, our former studies on the convenient synthesis of 3-position functionalized isoindolinone derivatives provided a basis for the efficient transformation of fused morpholines and isochromenopyridinones.¹³ Herein, we report an efficient synthesis method for 3-ethoxy/hydroxy-3,4-dihydro-6H-[1,4]-oxazino-[3,4-a]-isoindol-6-ones and 6H-isochromeno-[4,3-b]-pyridin-6-ones via acid-catalyzed intramolecular reactions of isoindolinones under mild conditions.

Scheme 1 Synthetic approaches toward fused morpholines and isochromenopyridinones.

Results and discussion

According to the previous methods developed by our group,¹³ the starting materials N-acetal-substituted-3-acyl isoindolinones (1) are readily available from a one-pot reaction of o-lithiated aromatic imines with carbon monoxide followed by the use of acyl chlorides as the electrophiles under mild reaction conditions on a gram scale (see the ESI†). With compounds 1 in hand, we were able to explore their reactivity under acid-catalyzed conditions (Table 1). When 1b was treated with trifluoromethanesulfonic acid (TfOH) in dichloromethane, dichloroethane or toluene (entries 1–3), 2b was obtained as the main product, and a trace amount of 3b could be detected by TLC. Using dichloromethane as the solvent, we selectively synthesized compound 2b with the highest yield (74%, entry 1). However, in solvent THF, 3b became the main product, no 2b was detected (entry 4), and the above results show a direct influence of the solvent on the formation of final products. In addition, when the acid was changed to concentrated sulfuric acid and THF was used as the solvent, the yield of 3b increased to 60% along with the extension of the reaction time (entry 8), which provides a method for the selective synthesis of 3b. Acetic acid could not catalyze this reaction (entry 11). p-Toluenesulfonic acid (pTSA) and AlCl₃ could catalyze this reaction, but the selectivity of 2b and 3b was poor (entries 12 and 13).

Table 1 Intramolecular cyclization of 1b ^a

Entry	Acid	Solvent	Time	2b ^f (%)	3b ^f (%)
a Reaction conditions: all reactions were performed with 1b (0.5 mmol, 1.0 equiv.), acid (1.0 or 8.0 equiv.) and solvent (25 mL) in a round bottom flask at room temperature under air conditions. b 1.0 equiv. c 8.0 equiv. d Detected by TLC. e Isolated unconverted 1b (21%). f Isolated yield based on 1b.
1	TfOH	CH 2 Cl 2	1 min	74	Trace
2	TfOH^b	ClCH2CH2Cl	1 min	48	Trace^d
3	TfOH^b	Toluene	1 min	50	Trace^d
4	TfOH^b	THF	1 min	0	43
5	TfOH^b	CH2Cl2	12 h	50	Trace^d
6	TfOH^b	Toluene	4 h	48	Trace^d
7	H2SO4^c	CH2Cl2	12 h	Trace^d	Trace^d
8	H 2 SO 4	THF	12 h	0	60
9	H2SO4^b	THF	12 h	0	38^e
10	CF3COOH^b	CH2Cl2	12 h	26	45
11	CH3COOH^b	CH2Cl2	12 h	0	0
12	pTSA^b	CH2Cl2	12 h	49	42
13	AlCl3^b	CH2Cl2	12 h	43	33

---

With the established optimal conditions, compounds 2 were selectively obtained by treating compounds 1 with TfOH in dichloromethane. This rapid and mild reaction shows broad substrate scope. As shown in Table 2, alkyl (2a–2d), benzyl (2e), phenyl (2f), electron-donating aryl (2g), electron-withdrawing aryl (2h), and furanyl (2i) are all compatible, generating the fused morpholine derivatives in yields of 57–97%. Electron-donating methoxy (2j–2m) and electron-withdrawing fluorine (2n–2q) on the isoindolinone ring are tolerable with yields of 72–86% and 78–97%, respectively.

Table 2 Synthesis of 3-ethoxy-3,4-dihydro-6H-[1,4]-oxazino-[3,4-a]-isoindol-6-ones (2)

---

Compounds 3 are obtained under the optimal conditions by treating 1 with concentrated sulfuric acid in THF. This reaction also shows broad substrate scope. As shown in Table 3, alkyl (3a–3d), benzyl (3e), phenyl (3f), electron-donating aryl (3g), electron-withdrawing aryl (3h), and heterocyclic furanyl (3i) are all compatible, leading to the synthesis of fused morpholines with a hemiacetal structure in yields of 60%–82%. Electron-donating methoxy on the isoindolinone ring is tolerable with yields of 51%–77% (3j–3m), and electron-withdrawing fluorine is also compatible with yields of 47–95% (3n–3q). Moreover, compound 3g can be obtained through a “one-pot” method starting from o-bromobenzaldehyde imine with a yield of 42%, namely the isolation of the starting material 1g is not necessary (Scheme 2).

Scheme 2 One-pot synthesis of 3g.

Table 3 Synthesis of 3-hydroxy-3,4-dihydro-6H-[1,4]-oxazino-[3,4-a]-isoindol-6-ones (3)

---

Surprisingly, 2b cannot be transformed into 3b irrespective of whether water is added or not under the conditions listed in Table 3, and the results show that the acetal structure of 2b is considerably stable under these reaction conditions. Although compounds 1 are potential precursors for the intramolecular aldol reaction,¹⁴ a rearrangement reaction is observed instead of only the aldol reaction. When TfOH was added to a toluene (Tol) solution of 1b, rapid formation of 2b was observed (entry 3, Table 1). With the increase of reaction temperature, 2b was transformed into 3b, which subsequently underwent an intramolecular rearrangement to produce compound 4b in 40% overall yield (Scheme 3). However, a similar reaction of 1e gave 3e as the major product in 53% yield, along with the desired rearrangement product 4i in only 10% yield. We also found that 3e was considerably stable, and the conversion of 3e into 4i hardly occurred under a heated TfOH/toluene system. However, the direct conversion of 3b into 4b was successful under such conditions, which gave 4b in 67% yield (Table 4). At the same time, the rearrangement products 4a and 4c–4f were also obtained from the corresponding hemiacetals 3 under a heated TfOH/toluene system in good to excellent yields. To our surprise, the rearrangement reaction of 3e to 4i occurred in 32% yield when concentrated sulfuric acid was used instead of TfOH. Compounds 4g, 4h, 4j and 4k were also obtained in good yields under a heated concentrated H₂SO₄/toluene system. Different acids possibly affect the equilibrium of hemiacetal to aldehyde, which subsequently undergoes a tandem aldol/rearrangement reaction to generate isochromenopyridinones 4 (Scheme 4).¹¹

Scheme 3 The intramolecular rearrangement of 1b and 1e.

Scheme 4 Proposed reaction mechanism.

Table 4 Synthesis of 6H-isochromeno-[4,3-b]-pyridin-6-ones (4)

a From TfOH. b From concentrated H₂SO₄.

---

To prove the practical application value of this method, amplification experiments were done where 1a was used as the starting material (Scheme 5). Compounds 3a (65%) and 4a (73%) were obtained on a gram scale.

Scheme 5 Gram-scale synthesis of 3a and 4a.

It is known that hemiacetal hydroxyl is an active functional group, so compounds 3 are anticipated to show great potential in other organic transformations. For example, the Ritter reaction of 3f with acetonitrile was achieved, which afforded compound 5 in 68% yield (Scheme 6). In addition, the esterification reaction of 3f was also successful (Table 5), which gave potential biologically active compounds 6.¹⁵

Scheme 6 The Ritter reaction of 3f with CH₃CN.

Table 5 The esterification reactions of 3f

---

To evaluate the biological activities of compounds, the fungicidal activities of compounds against Alternaria solani (A. s), B. cinerea (B. c), Cercospora arachidicola (C. a), F. graminearum (F. g), Physalospora piricola (P. p), R. solani (R. s), and Sclerotinia sclerotiorum (S. s) were preliminarily evaluated in vitro (Table 6).¹⁶ The bioassay results indicated that compounds 2g, 2n, 4g, 4h and 4k exhibited good activities against the above-mentioned phytopathogens in inhibiting mycelial growth at a concentration of 50 μg mL⁻¹. The activities of 6b and 6c against Hyaloperonospora arabidopsidis on Arabidopsis thaliana showed good systemical acquired resistance activities in vivo (Fig. 2),¹⁷ which highlights the important value of this investigation.

Fig. 2 Compounds enhanced the resistance of A. thaliana against H. arabidopsidis Noco2. (A) Sporulation level of H. arabidopsidis Noco2 of WT, spraying-inoculated with H. arabidopsidis Noco2 at 24 h after treatment with 100 μM 6a, 6b, 6c or BTH. (B) Photos of A. thaliana treated with 6a (named 6-89 in photos), (C) photos of A. thaliana treated with 6b (named 6-90 in photos) and (D) photos of A. thaliana treated with 6c (named 6-91 in photos).

Table 6 In vitro fungicidal activity of compounds at 50 μg mL⁻¹ (%)

Compound	A. s	B. c	C. a	F. g	P. p	R. s	S. s
2a	22 ± 1	8 ± 1	19 ± 2	29 ± 2	12 ± 1	30 ± 1	13 ± 1
2b	16 ± 1	0	13 ± 2	24 ± 2	2 ± 1	25 ± 1	14 ± 3
2c	0 ± 3	0	7 ± 1	9 ± 1	0	12 ± 3	0 ± 2
2d	12 ± 1	0	5 ± 1	34 ± 1	7 ± 1	27 ± 1	15 ± 3
2e	29 ± 2	0	23 ± 1	37 ± 1	16 ± 3	24 ± 2	36 ± 2
2f	25 ± 3	20 ± 3	25 ± 1	47 ± 2	22 ± 0	27 ± 3	33 ± 3
2g	57 ± 1	42 ± 1	55 ± 1	74 ± 0	48 ± 1	52 ± 1	66 ± 1
2h	48 ± 1	55 ± 1	34 ± 1	63 ± 1	35 ± 2	39 ± 1	35 ± 2
2i	13 ± 2	0	10 ± 1	22 ± 0	0	22 ± 2	20 ± 1
2j	22 ± 1	5 ± 1	17 ± 1	20 ± 2	11 ± 2	18 ± 1	21 ± 0
2k	27 ± 1	31 ± 1	53 ± 0	72 ± 1	52 ± 1	57 ± 1	65 ± 1
2l	26 ± 1	27 ± 1	25 ± 1	31 ± 1	13 ± 2	24 ± 1	27 ± 1
2m	17 ± 1	26 ± 1	27 ± 1	33 ± 2	14 ± 2	26 ± 1	18 ± 3
2n	67 ± 2	40 ± 2	57 ± 2	72 ± 1	45 ± 1	65 ± 2	70 ± 1
2o	15 ± 1	0	27 ± 1	29 ± 1	24 ± 1	20 ± 1	26 ± 2
2p	7 ± 1	0	20 ± 2	21 ± 2	16 ± 3	17 ± 1	27 ± 1
2q	11 ± 1	6 ± 1	15 ± 4	17 ± 2	10 ± 2	27 ± 1	14 ± 2
3a	2 ± 3	0	17 ± 2	33 ± 1	4 ± 3	29 ± 3	23 ± 3
3b	10 ± 1	0	19 ± 3	30 ± 1	5 ± 3	28 ± 1	18 ± 1
3c	12 ± 0	27 ± 0	16 ± 4	16 ± 1	8 ± 1	28 ± 0	14 ± 2
3d	10 ± 1	19 ± 1	9 ± 1	11 ± 3	13 ± 5	22 ± 1	14 ± 2
3e	49 ± 1	0	28 ± 2	38 ± 1	9 ± 1	28 ± 1	27 ± 1
3f	25 ± 1	0	23 ± 1	70 ± 6	24 ± 0	29 ± 1	23 ± 1
3g	18 ± 1	0	11 ± 1	63 ± 1	14 ± 1	15 ± 1	15 ± 3
3h	36 ± 1	1 ± 1	20 ± 2	70 ± 1	30 ± 1	30 ± 1	31 ± 1
3i	27 ± 1	0	22 ± 3	29 ± 1	2 ± 2	19 ± 1	15 ± 1
3j	27 ± 1	31 ± 1	18 ± 1	32 ± 2	10 ± 2	33 ± 1	15 ± 1
3k	23 ± 1	0	13 ± 2	13 ± 2	1 ± 2	18 ± 1	18 ± 1
3l	31 ± 1	26 ± 1	21 ± 1	21 ± 1	9 ± 2	22 ± 1	25 ± 1
3m	31 ± 2	0	10 ± 1	8 ± 2	15 ± 2	9 ± 2	18 ± 1
3n	34 ± 1	0	19 ± 2	42 ± 1	12 ± 3	27 ± 1	23 ± 1
3o	26 ± 1	0	13 ± 1	27 ± 0	4 ± 3	15 ± 1	22 ± 2
3p	33 ± 1	49 ± 1	13 ± 1	26 ± 3	16 ± 2	19 ± 1	19 ± 2
3q	30 ± 1	38 ± 1	8 ± 2	22 ± 2	11 ± 1	18 ± 1	19 ± 2
4a	48 ± 1	42 ± 1	33 ± 0	41 ± 3	36 ± 0	61 ± 0	25 ± 0
4b	51 ± 0	56 ± 0	30 ± 0	49 ± 2	43 ± 0	64 ± 0	33 ± 0
4c	30 ± 0	20 ± 9	17 ± 1	33 ± 2	35 ± 1	34 ± 0	23 ± 1
4d	52 ± 0	33 ± 2	36 ± 0	64 ± 4	69 ± 1	64 ± 0	55 ± 1
4e	53 ± 2	51 ± 2	73 ± 2	0	55 ± 2	73 ± 1	46 ± 2
4f	57 ± 0	17 ± 2	58 ± 1	21 ± 2	48 ± 0	69 ± 0	53 ± 2
4g	66 ± 0	73 ± 2	43 ± 2	66 ± 0	53 ± 0	71 ± 0	50 ± 2
4h	52 ± 1	89 ± 1	78 ± 1	30 ± 1	66 ± 1	76 ± 1	51 ± 1
4i	13 ± 0	39 ± 0	15 ± 0	31 ± 2	22 ± 1	28 ± 1	3 ± 0
4j	13 ± 0	29 ± 2	21 ± 0	33 ± 2	3 ± 3	24 ± 4	3 ± 0
4k	53 ± 2	51 ± 2	75 ± 1	0	62 ± 2	70 ± 1	46 ± 2
6a	25 ± 5	82 ± 2	15 ± 1	17 ± 0	16 ± 1	25 ± 1	30 ± 1
6b	23 ± 9	60 ± 3	18 ± 1	13 ± 0	15 ± 1	23 ± 5	16 ± 1
6c	19 ± 4	80 ± 1	20 ± 1	24 ± 0	22 ± 2	35 ± 1	25 ± 0
BTH	13 ± 2	14 ± 8	18 ± 0	12 ± 1	19 ± 1	74 ± 1	5 ± 1

---

Conclusions

In summary, we developed new approaches for the synthesis of bioactive leads with systemical acquired resistance by fusing morpholines and isochromenopyridinones via acid-catalyzed intramolecular tandem reactions of isoindolinone derivatives. The methods are simple and efficient with broad substrate scope and good to excellent yields. The protocol is easy to apply at the gram level and is helpful for further lead modification of these bioactive derivatives in the areas of pharmacy and agrochemistry.

Author contributions

Xiaoyu Liu: investigation, methodology, bioactivity test, and writing – original draft and editing; Yaru Sun: methodology; Shuang Hong, Xia Ji, Wei Gao, Haolin Yuan, Yue Zhang and Bin Lei: bioactivity test; Liangfu Tang and Zhijin Fan: project administration, supervision, funding acquisition and writing – review & editing.

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

This work was supported in part by the National Key Research and Development Program of China (no. 2022YFD1700400 and 2022YFD1700402); the Tianjin Natural Science Foundation (no. 21JCZXJC00110); the Frontiers Science Center for New Organic Matter, Nankai University (no. 63181206); and the Key Research and Development Program of Xinjiang Uygur Autonomous Region (no. 2022B02001).

References

1. (a) E. Valencia, I. Weiss, S. Firdous, A. J. Freyer, M. Shamma, A. Urzús and V. Fajardo, Tetrahedron, 1984, 40, 3957; (b) D. L. Comins, S. Schilling and Y. Zhang, Org. Lett., 2005, 7, 95.
2. (a) S. Atarashi, S. Yokohama, K. Yamazaki, K. Sakano, M. Imamura and I. Hayakawa, Chem. Pharm. Bull., 1987, 35, 1896; (b) V. R. Anderson and C. M. Perry, Drugs, 2008, 68, 535.
3. (a) S. C. Bobzin and D. J. Faulkner, J. Org. Chem., 1991, 56, 4403; (b) Y. Wang, W. Y. Zhang and S. L. You, J. Am. Chem. Soc., 2019, 141, 2228; (c) S. M. S. Atta, D. S. Farrag, A. M. K. Sweed and A. H. Abdel-Rahman, Eur. J. Med. Chem., 2010, 45, 4920; (d) L. A. Baltina, H. C. Lai, Y. C. Liu, S. H. Huang, M. J. Hour, L. A. Baltina, T. R. Nugumanov, S. S. Borisevich, L. M. Khalilov, S. F. Petrova, S. L. Khursan and C. W. Lin, Bioorg. Med. Chem., 2021, 41, 116204.
4. X.-G. Tong, L.-L. Zhou, Y.-H. Wang, C. Xia, Y. Wang, M. Liang, F.-F. Hou and Y.-X. Cheng, Org. Lett., 2010, 12, 1844.
5. (a) Z. Mao, W. Sun, L. Fu, H. Luo, D. Lai and L. Zhou, Molecules, 2014, 19, 5088; (b) H. Wang, Y. Guo, Z. Luo, L. Gao, R. Li, Y. Zhang, H. M. Kalaji, S. Qiang and S. Chen, J. Fungi, 2022, 8, 168.
6. (a) X. Ren, M. E. Kondakova, D. J. Giesen, M. Rajswaran, M. Madaras and W. C. Lenhart, Inorg. Chem., 2010, 49, 1301; (b) M. J. Jurow, C. Mayr, T. D. Schmidt, T. Lampe, P. I. Djurovich, W. Brütting and M. E. Thompson, Nat. Mater., 2016, 15, 85.
7. (a) R. Wijtmans, M. K. S. Vink, H. E. Schoemaker, F. L. van Delft, R. H. Blaauw and F. P. J. T. Rutjes, Synthesis, 2004, 641; (b) J. Ilaš, P. Š. Anderluh, M. S. Dolenc and D. Kikelj, Tetrahedron, 2005, 61, 7325; (c) V. A. Pal'chikov, Russ. J. Org. Chem., 2013, 49, 787; (d) A. Tzara, D. Xanthopoulos and A. P. Kourounakis, ChemMedChem, 2020, 15, 392.
8. (a) F. Foschi, D. Albanese, I. Pecnikaj, A. Tagliabue and M. Penso, Org. Lett., 2017, 19, 70; (b) J. V. Matlock, T. D. Svejstrup, P. Songara, S. Overington, E. M. McGarrigle and V. K. Aggarwal, Org. Lett., 2015, 17, 5044; (c) J. Zhou and Y.-Y. Yeung, J. Org. Chem., 2014, 79, 4644; (d) E. Lenci, A. Rossi, G. Menchi and A. Trabocchi, Org. Biomol. Chem., 2017, 15, 9710.
9. (a) K. E. Soklou, H. Marzag, B. Vallée, S. Routier and K. Plé, Adv. Synth. Catal., 2022, 364, 218; (b) M. Borah, U. Borthakur and A. K. Saikia, J. Org. Chem., 2017, 82, 1330; (c) T. Biberger, S. Makai, Z. Lian and B. Morandi, Angew. Chem., Int. Ed., 2018, 57, 6940; (d) M. U. Luescher, C.-V. T. Vo and J. W. Bode, Org. Lett., 2014, 16, 1236; (e) C. Jindakun, S.-Y. Hsieh and J. W. Bode, Org. Lett., 2018, 20, 2071; (f) Y. Y. Lau, H. Zhai and L. L. Schafer, J. Org. Chem., 2016, 81, 8696; (g) S. A. Ruider, S. Müller and E. M. Carreira, Angew. Chem., Int. Ed., 2013, 52, 11908.
10. (a) M. C. D. Fürst, L. R. Bock and M. R. Heinrich, J. Org. Chem., 2016, 81, 5752; (b) S. Crespi, S. Jäger, B. König and M. Fagnoni, Eur. J. Org. Chem., 2017, 2147.
11. M. Othman, P. Pigeon and B. Decroix, Tetrahedron, 1998, 54, 8737.
12. (a) R. Savela and C. Méndez-Gálvez, Chem. – Eur. J., 2021, 27, 5344; (b) S. Samanta, S. A. Ali, A. Bera, S. Giri and K. Samanta, New J. Chem., 2022, 46, 7780; (c) Z. Xie, L. Jin, H. Li, J. Meng and Z. Le, Synthesis, 2023, 3172; (d) M. K. Gupta, A. Panda, S. Panda and N. K. Sharma, Org. Biomol. Chem., 2023, 21, 5104; (e) C. Wiethan, I. B. Braga, V. H. Menezes da Silva, J. M. Batista Jr. and C. R. D. Correia, ChemCatChem, 2023, 15, e2023004; (f) T. Ma, J. Hua, M. Bian, H. Qin, X. Lin, X. Yang, C. Liu, Z. Yang, Z. Fang and K. Guo, Org. Chem. Front., 2022, 9, 25; (g) X. Du, Y. Hu, D. Yang, D. Huang, W. Yang, H. Wu and H. Zhao, Org. Biomol. Chem., 2022, 20, 783.
13. (a) H.-J. Li, Y.-Q. Zhang and L.-F. Tang, Tetrahedron, 2015, 71, 7681; (b) Y. Xu, X.-Y. Liu, Z.-H. Wang and L.-F. Tang, Tetrahedron, 2017, 73, 7245; (c) X.-Y. Liu, X.-M. Luo and L.-F. Tang, Tetrahedron, 2020, 76, 131341.
14. Y. Quevedo-Acosta, I. D. Jurberg and D. Gamba-Sánchez, Org. Lett., 2020, 22, 239.
15. (a) M. Oostendorp, W. Kunz, B. Dietrich and T. Staub, Eur. J. Plant Pathol., 2001, 107, 19; (b) K. Tsubata, K. Kuroda, Y. Yamamoto and N. Yasokawa, J. Pestic. Sci., 2006, 31, 161; (c) Z. J. Fan, Z. G. Shi, H. K. Zhang, X. F. Liu, L. L. Bao, L. Ma, X. Zhou, Q. X. Zheng and N. Mi, J. Agric. Food Chem., 2009, 57, 4279; (d) Y. Bektas and T. Eulgem, Front. Plant Sci., 2015, 5, 804; (e) M. Markiewicz, P. Lewandowski, M. Spychalski, R. Kukawka, J. Feder-Kubis, S. Beil, M. Smiglak and S. Stolte, Green Chem., 2021, 23, 5138; (f) Y. Zhang, K. Li, W. Gao, X. Liu, H. Yuan, L. Tang and Z. Fan, Org. Lett., 2022, 24, 6599.
16. Z. Hao, W. Wang, B. Yu, X. Qi, Y. Lv, X. Liu, H. Chen, T. A. Kalinina, T. V. Glukhareva and Z. Fan, Chin. J. Chem., 2021, 39, 1531.
17. (a) K. A. Lawton, L. Friedrich, M. Hunt, K. Weymann, T. Delaney, H. Kessmann, T. Staub and J. Ryals, Plant J., 1996, 10, 71; (b) X. Qi, K. Li, L. Chen, Y. Zhang, N. Zhang, W. Gao, Y. Li, X. Liu and Z. Fan, Int. J. Mol. Sci., 2022, 23, 5348; (c) X. Qi, L. Chen, Y. Zhang, W. Gao, L. Chen, D. Wang, L. Tang, Z. Wang, N. N. Wang and Z. Fan, J. Agric. Food Chem., 2022, 70, 3142.

---

Footnote

† Electronic supplementary information (ESI) available. CCDC 2298345 and 2298279. For ESI and crystallographic data in CIF or other electronic format see DOI: https://doi.org/10.1039/d3ob01717f

---